%0 Journal Article
%T Regulation of TGF-¦Â receptor activity
%A Fei Huang
%A Ye-Guang Chen
%J Cell & Bioscience
%D 2012
%I BioMed Central
%R 10.1186/2045-3701-2-9
%X Transforming growth factor-¦Â (TGF-¦Â) family, including TGF-¦Â, activin, Nodal, bone morphogenetic proteins (BMPs) and others, play vital roles in development, tissue homeostasis and some diseases development [1-3]. TGF-¦Â signaling is initiated by the binding of TGF-¦Â to its serine and threonine kinase receptors, the type II (T¦ÂRII) and type I (T¦ÂRI) receptors on the cell membrane. Ligand binding leads to formation of the receptor heterocomplex, in which T¦ÂRII phosphorylates threonine and serine residues in the TTSGSGSG motif of T¦ÂRI and thus activates T¦ÂRI [2,4]. The activated T¦ÂRI recruits and phosphorylates the R-Smad proteins, Smad2/3 for TGF-¦Â and activin signaling while Smad1/5/8 for BMP signaling, which then form a heterocomplex with the Co-Smad Smad4 [5,6]. The Smad complexes are then translocated into the nucleus to regulate transcription of the target genes in cooperation with other co-factors [5,7,8]. For each member of the TGF-¦Â family, they have their own type I and type II receptors. Among the seven type I receptors, which are also called as activin receptor-like kinases (ALKs), T¦ÂRI/ALK5 can mediate TGF-¦Â signaling with the TGF-¦Â type II receptor T¦ÂRII to activate Smad2/3 in universal cell types, while in endothelial cells ALK1 functions with T¦ÂRII to activate Smad1/5/8 for TGF-¦Â signaling [8-10]. In response to BMPs, ALK2/3/6 can activate Smad1/5/8 with the type II receptors BMPRII, ActRII and ActRIIB [11,12]. ALK4/7 can activate Smad2/3 with ActRII and ActRIIB to mediate activin/Nodal signaling [13]. In this review, we mainly discuss the regulation mechanisms of TGF-¦Â signaling receptors.In addition to activating Smad2/3, TGF-¦Â can also activate mitogen-activating protein kinases (MAPKs) (ERK, p38 and JNK), phosphatidylinositol 3 kinase (PI3K)/Akt and small GTPases in a context-dependent manner [14-17]. Furthermore, despite the fact that TGF-¦Â can activate Smad1/5/8 in endothelial cells which requires ALK1 [18,19], it can also activate Smad1/5/8 in ot
%K TGF-¦Â receptor
%K phosphorylation
%K ubiquitination
%K degradation
%U http://www.cellandbioscience.com/content/2/1/9